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This paper presents a current situation of studies and applications which are using serious games and artificial intelligence (AI) in rehabilitation of rheumatoid arthritis, and possible future directions. The objectives of this paper are: to highlight the technologies used for recovery of patients with rheumatoid arthritis (RA), to summarize the state of the art of existing applications and to present the authors work, a software application that aims contributing to the recovery of the specific patients. At this stage the application was tested by a group of 10 patients from Medical Centre Sf. Mary of Timisoara. Most of the patients reported that the physical and psychical effort were between easy-very easy. The patients confirmed that they would use the application in their rehabilitation process and are very excited about this type of rehabilitation that stimulates curiosity and a state of wellbeing. The application works based on the leap motion device that proved to be the most suitable device in terms of precision and the manner of interaction in virtual reality games.

Background/Aims To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. Results The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. Conclusions Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.

Background Rheumatoid arthritis interstitial lung disease (RA-ILD) is one of the most common complications of rheumatoid arthritis (RA) that severely impairs the quality of life and survival. Zang Bi Formula (ZBF) is mostly used in clinical practice for patients with recurrent occurrence of RA. However, its mechanism of action and efficacy in RA-ILD still remain unclear. Objective To investigate the therapeutic possibilities and potential mechanisms of the ZBF on RA and RA-ILD. Objective To investigate the therapeutic possibilities and potential mechanisms of the ZBF on RA and RA-ILD. Methods From January 2022 to March 2023, a total of 14 tumor necrosis factor alpha-transgenic (TNF-Tg) mice were randomly divided into Saline group and ZBF group, with 7 mice in each group. At the same time, 7 wild-type (WT) mice in the same litter were randomly selected as the control group (WT group). Intragastric administration of ZBF 1.4 g/mL with 0.2 mL per time was given to mice of ZBF group once a day, and those in the WT group and Saline group were given an equal amount of normal saline via intragastric administration. After the intervention for 8 weeks, hematoxylin&eosin (H&E) staining of mouse ankle tissues was performed to observe the inflammatory cell area. Alcian blue-orange and tartrate-resistant acid phosphatase (TRAP) staining was performed to observe the cartilage area and bone area ratio, as well as the osteoclast area, respectively. The area proportion of inflammatory cells, fibrosis and T-cell/B-cell proportion in mouse lung tissues were observed by H&E staining, Masson staining and immunofluorescence staining, respectively. Results Mice in the Saline group had significantly increased inflammatory cell infiltration, synovial hyperplasia, and ankle tissue destruction. Inflammation of the ankle joint was alleviated in the ZBF group. The proportion of inflammatory cells in the Saline group was significantly higher than that of the ZBF group and WT group, which was significantly higher in the ZBF group than that of the WT group (P

Rheumatoid arthritis (RA) is a refractory autoimmune disease with chronic and systemic characteristics, however, the pathogenesis of this disease has not been fully defined. Autophagy is a metabolic process that exists in eukaryotic cells and maintains normal physiological activities and cell homeostasis. Dysregulation of autophagy is related to the occurrence and development of various diseases such as RA. The databases of CNKI, Wanfang Data, VIP, PubMed, Web of Science, Elsevier, etc. were searched for the literature related to autophagy in RA pathogenesis. The role of autophagy in the pathogenesis of RA was summarized in terms of maintaining synovial inflammation (improving anti-apoptosis rate of synovial cells and regulating the phenotype transformation of synovial cells), promoting bone destruction (participating in osteoclastogenesis and regulating chondrocyte apoptosis) and disrupting immune system homeostasis (regulating the activation and maturation of immune cells, participating in the presentation of citrullinated proteins, and inducing carbamoylation of proteins), in order to provide basis and reference for the pathogenesis research and treatment of RA.

Background/Aims This study aims to evaluate the incidence of malignancy in patients with rheumatoid arthritis (RA) and to investigate risk factors for such in a nationwide, population-based cohort. Methods In a large, prospective, observational cohort study, 5,077 patients with RA were enrolled from July 2009 to December 2011 and followed until February 2017. Standardized incidence ratios (SIRs) for malignancy were calculated using age- and sex-specific cancer rates in the Korean general population. Poisson regression was used to identify the risk of incident malignancy. Results The cohort included 5,023 participants with RA contributing 16,689 person-years of follow-up. A total of 148 malignancies were recorded. The risks of stomach cancer (SIR, 0.41; 95% confidence interval [CI], 0.21 to 0.74), colon cancer (SIR, 0.13; 95% CI, 0.03 to 0.37), and lung cancer (SIR, 0.35; 95% CI, 0.14 to 0.72) were lower in RA patients than in the general population. Poisson regression modeling demonstrated that the malignancy risk was more than two-fold greater in patients with thyroid disease than in those without thyroid disease. Hydroxychloroquine therapy was associated with a reduced risk (relative risk, 0.39; 95% CI, 0.189 to 0.801) of malignancy development. Conclusions The overall risk of malignancy in patients with RA is decreased relative to in the general population. In particular, stomach, colon, and lung cancers in Korean RA patients are less common, while brain and central nervous system cancers in male RA patients are more frequent. The patients with thyroid disease and longer RA disease duration were at increased risk for developing malignancy, while hydroxychloroquine users were at lower risk.

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a ubiquitously expressed intracellular signal transduction pathway involved in cell proliferation, differentiation, apoptosis, immune regulation and other biological processes. Existing evidence indicates that continuous activation of this signaling pathway is closely related to the pathogenesis and clinical manifestations of many autoimmune rheumatic diseases. We reviewed the latest advances in mechanisms of JAK/STAT signal transduction, and the roles of the pathway in development of autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, and gout, suggesting that JAK/STAT signaling pathway may be a therapeutic target for autoimmune rheumatic diseases, which may offer new ideas and directions for clinical treatment.

Background/Aims This study was performed to undertake cross-cultural adaptation and validation of the Educational Needs Assessment Tool (ENAT) in rheumatoid arthritis (RA) for use in Korea. Methods The study involved two main phases: cross-cultural adaptation of the ENAT from English into Korean, and validation of the Korean ENAT. The first phase followed the established process of cross-cultural adaptation of self-report measures, and in the second phase, the Korean ENAT data were analyzed using the Rasch measurement model. Fit to the model was determined using the observed data infit and outfit statistics. Additional tests of validity included unidimensionality and internal consistency. Results Adequate conceptual equivalence was achieved following the adaptation process. A total of 123 patients completed the Korean ENAT. The mean age was 46.7 ± 12.3 years and the majority of patients (81.3%) were female. Thirty-five of the 39 items gave good fit to the model. The four items deviating from the model had infit and outfit > 1.50. The item separation index (5.26) and item reliability index (0.97) provided evidence for good reliability of items. All seven domains of the Korean ENAT fit the Rasch model. The internal consistency of the Korean ENAT was high, and unidimensionality was confirmed (person separation index, 3.41; reliability index, 0.92; item separation index, 16.82; reliability index, 1.00). Conclusions Using the standard procedure for cross-cultural adaptation, the ENAT has been adapted into Korean, and Rasch analysis has confirmed the construct validity, reliability, and unidimensionality of the Korean ENAT.

ABSTRACT BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease with higher prevalence among women aged between 30 and 50 years and general prevalence of 1% worldwide. Interventions promoting improvement of quality of life for individuals with RA are required. Tai Chi appears to be a low-cost alternative, with studies showing positive results from this technique. However, regarding aspects of RA such as pain and sensitivity, studies remain inconclusive. OBJECTIVES: To compare the effectiveness of the Tai Chi method for treating patients diagnosed with rheumatoid arthritis, among systematic reviews. DESIGN AND SETTING: Overview of systematic reviews with Cochrane and non-Cochrane methodology. METHODS: Systematic reviews involving quasi-randomized and randomized clinical trials (RCTs) on use of Tai Chi, with no restrictions regarding the date and language of publication, were included. RESULTS: Three systematic reviews were included. The effects of Tai Chi associated with education and stretching exercises versus education and stretching were evaluated in these reviews. They showed that improvements in the variables of mood, depression and functional index were associated with use of Tai Chi. CONCLUSIONS: The findings suggest that clinical improvement was achieved, although not statistically significant with regard to pain and disease pattern, as assessed using the ACR20 measurement. Improvements relating to disability and quality of life were also seen. There was a low level of evidence and therefore caution in data analysis is recommended. The three studies included showed poor reliability for providing an accurate and complete summary of use of Tai Chi among people diagnosed with rheumatoid arthritis. PROSPERO: CRD42019125501.

ABSTRACT Objective To evaluate the therapeutic response (functionality) and its associated factors in patients on biological drugs on the Public Health System for treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Methods An open prospective cohort was carried out from 2011 to 2019, in Belo Horizonte (MG). Functionality was assessed using the Health Assessment Questionnaire Disability-Index at baseline, and after 6 and 12 months of follow-up. Factors associated with poor functionality were identified through logistic regression. Results The median Health Assessment Questionnaire Disability-Index at baseline was 1.5 (interquartile range of 0.8-1.9), with poor functionality observed in patients with rheumatoid arthritis. Improved functionality was seen at 6 months of treatment for the three diseases. The predictors of poor functionality at 6 months for psoriatic arthritis and ankylosing spondylitis were female sex, low education levels, and high disease activity; and for rheumatoid arthritis and psoriatic arthritis were female sex, advanced age, and high disease activity. In 12 months, the three diseases had predictors of worse functionality: female sex, low education, and high disease activity. Conclusion There was a significant improvement in functionality during the follow-up, with better response at 6 months of treatment. Poor functionality was observed in older, female patients, with low education and high disease activity.

Background/Aims Safety for tumor necrosis factor inhibitors (TNFi) in cancer has been focused on risk of incident malignancies, but studies on prognostic effects have been scarce. We determined survival and recurrence rates at 1, 2, and 5 years after cancer diagnosis in patients with and without concurrent TNFi use. Methods Chart reviews were performed between 1996 and 2015 at the VA North Texas Healthcare System. Cases were patients with inflammatory disease, concomitant malignancy, and TNFi use while controls were patients with inflammatory disease, concomitant malignancy but no TNFi use. Cases and controls were matched for type of malignancy. Analysis was performed with log-rank tests on Kaplan-Meier curves. Results Thirty-six cases and 72 controls were identified. For cases, survival at 1, 2, and 5 years were 32 (89%), 31 (86%), and 29 (81%) compared to 63 (90%), 61 (87%), and 51 (73%) for the control group (P=0.985). For cases, recurrence rates at 1, 2, and 5 years were 3 (8%), 5 (14%), and 6 (17%) compared to 2 (3%), 5 (7%), and 7 (10%) for the control group (P=0.158). Conclusions Our findings suggest TNFi may be safely used in select inflammatory disease patients with concurrent cancer if therapy is needed for proper disease control. However, case-by-case consideration in conjunction with an oncologist is recommended while considering the apparent safety of TNFi for patients suffering from active inflammatory diseases despite having a concomitant malignancy.

Background/Aims Biologics are very effective drugs for patients with ankylosing spondylitis (AS). However, there are patients who are not responding to biologics. This study aimed to evaluate the level of tumor necrosis factor α (TNF-α), interleukin (IL)-23, and IL-17 from synovial fluid in patients with AS and rheumatoid arthritis (RA) and differences of the level of those cytokines according to drugs. Methods Synovial fluid was obtained from 34 patients (42 samples) with AS and 45 patients (47 samples) with RA with active arthritis of the knee, and the cytokine levels were measured. The differences in the levels between patients treated with and without biologics (biologics and non-biologics groups, respectively) were analyzed in AS and RA. The correlations between cytokines were examined in the non-biologics and biologics groups. Results The TNF-α level in AS was significantly lower than that in RA (p = 0.016). The IL-17 and IL-23 levels were not different between AS and RA (p = 0.409 and p = 0.562, respectively). In AS and RA, TNF-α, IL-17, and IL-23 showed good correlation among each other in the non-biologics group. However, there was no significant correlation in biologics group. In some patients in the AS group, the IL-17 or IL-23 level was markedly elevated in the biologics group. Conclusions Treatment with biologics affects the cytokine profile in inflammatory synovial fluid in patients with both AS and RA. Furthermore, IL-23 and IL-17 cytokine might be an important factor in some patients who are unresponsive to biologics in AS.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthritis, and the complex interaction and activation of innate and adaptive immune cells are involved in RA pathogenesis. Mast cells (MCs) are one of the tissue-resident innate immune cells, and they contribute to RA pathogenesis. In the present review, the evidence of the pathologic role of MC in RA is discussed based on human and animal data. In addition, the potential role of MC in RA pathogenesis and the research area that should be focused on in the future are suggested.

Background/Aims The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. Methods This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. Results A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was –19.0 in the bDMARD group and –12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. Conclusions There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

Biological disease-modifying antirheumatic drugs (bDMARDs) are highly effective agents for the treatment of inf lammatory arthritis; however, they also possess a potential risk for serious infection. Recently, with the rapid expansion of the bDMARDs market in Korea, reports of serious adverse events related to the agents have also increased, necessitating guidance for the use of bDMARDs. Current work entitled, “Expert consensus for the use of bDMARDs drugs for inflammatory arthritis in Korea,” is the first to describe the appropriate use of bDMARDs in the management of inflammatory arthritis in Korea, with an aim to provide guidance for the local medical community to improve the quality of clinical care. Twelve consensus statements regarding the use of bDMARDs for the management of rheumatoid arthritis and ankylosing spondylitis were generated. In this review, we provide detailed guidance on bDMARDs use based on expert consensus, including who should prescribe, the role of education, indications for use, and monitoring strategies for safety.

Background/aims To examine the association between rheumatoid arthritis (RA) and periodontitis or tooth loss. Methods The study used data from the fifth and sixth Korea National Health and Nutrition Examination Surveys conducted from 2010 to 2015. RA was defined as participant-reported physician-diagnosed RA that was being treated. Periodontitis and the number of natural teeth were determined by dental examination. Periodontitis was defined according to the community periodontal index (periodontal probing depth ≥ 4 mm). The association between RA and periodontitis or tooth loss was examined after controlling for confounding variables (e.g., age, smoking status, socioeconomic status, dental caries, frequency of toothbrushing, body mass index, alcohol consumption, and diabetes) in men and women. Subgroup analyses stratified by age were also performed. Results The study enrolled 20,297 participants aged ≥ 19 years (157 RA patients and 20,140 non-RA controls). There was no association between RA and periodontitis or tooth loss in men and women. Subgroup analyses in those aged < 60 years revealed a non-significant association between RA and periodontitis (adjusted odds ratio, 1.53; p = 0.162), but they revealed a significant association between RA and tooth loss (adjusted β, 0.20; p = 0.042). Conclusions RA was not associated with periodontitis, but was associated with tooth loss in younger adults. Younger RA patients are more likely to suffer tooth loss than general younger population; thus dental management is required.

Clinical research is the study of aspects of patient health or illness that are closely related to clinical practice. In the late 20th and early 21th century, outcomes for patients with rheumatoid arthritis (RA) improved dramatically due to breakthroughs in new drugs. Patient-reported outcome measures now play a significant role in the drug development process as study endpoints in clinical trials of new therapies, and this has led to increased interest in the patient's perspective, drug safety and treatment outcomes in clinical practice. In accordance with these needs, many prospective cohorts for RA patients and registries of biologic disease modifying anti-rheumatic drugs have been actively conducted in the United States and European and Asian countries. A gradual shift is taking place in the major outcomes of clinical research using these prospective cohorts and registries. This article will introduce representative registries for RA in each country set up in the early 2000s and will discuss future perspectives in clinical research on RA patients using such clinical registries.

Background/Aims To identify the factors associated with time to diagnosis after symptom onset in patients with early rheumatoid arthritis (RA). Methods Early RA patients with ≤ 1 year of disease duration in the KORean Observational study Network for Arthritis (KORONA) database were included in this analysis. Patients were further divided into two groups according to the time to diagnosis from symptom onset: the early diagnosis group (time to diagnosis ≤ 1 year) and the late diagnosis group (time to diagnosis > 1 year). Using the multivariable regression model, we identified factors associated with early diagnosis. Results Among 714 early RA patients, 401 patients (56.2%) and 313 patients (43.8%) were included in the early diagnosis and late diagnosis groups, respectively. The mean disease duration was 0.47 years in the early diagnosis group and 0.45 years in the late diagnosis group. In multivariable model analysis, greater age at onset (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02 to 1.05), high school education or higher (OR, 1.68; 95% CI, 1.14 to 2.47), higher income (OR, 1.48; 95% CI, 1.05 to 2.08), and initial small joint involvement (OR, 1.42; 95% CI, 1.02 to 1.98) were factors associated with early diagnosis. At diagnosis, disease activity scores using 28 joints on diagnosis (3.81 ± 1.44 vs. 3.82 ± 1.42, p = 0.92) and functional disability (0.65 ± 0.61 vs. 0.57 ± 0.62, p = 0.07) did not different between the two groups. However, hand joint erosion on X-ray (37.8% vs. 25.6%, p < 0.01) was more common in the late diagnosis group than the early diagnosis group. Conclusions Older onset age, higher educational level and income, and initial small joint involvement were positive factors for early diagnosis of RA.

Background/Aims To investigate the efficacy and safety of tocilizumab (TCZ) humanized anti-interleukin-6 receptor monoclonal antibody, in Korean patients with active rheumatoid arthritis (RA) refractory to conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX) Methods The main study was a 24-week, randomized, double-blind, controlled trial that was followed by a 48-week, open-labeled, extension phase. TCZ (8 mg/kg) or placebo was intravenously administered every 4 weeks. Results Those treated with TCZ showed more favorable outcomes in terms of 20% according to the American College of Rheumatology response criteria (ACR20) and ACR50 responses, individual parameters of ACR core set, disease activity score in 28 joints (DAS28) remission, and European League Against Rheumatism (EULAR) response at week 24. These improvements were maintained or increased during the extension period. DAS28 remission at week 72 was associated with EULAR good response at week 12. The patients who experienced any adverse event (AE) were more frequent in the TCZ group compared to the placebo group. Most AEs were mild or moderate in intensity, although TCZ therapy had possible AEs including serious infection, abnormal liver function, and atherogenic lipid profile. Conclusions TCZ infusion add-on is highly efficacious and well-tolerated in Korean patients with active RA refractory to conventional DMARDs including MTX. EULAR good response at week 12 could predict DAS28 remission at week 72.

Background/Aims Magnetic resonance imaging (MRI) is a sensitive and useful method for the detection of synovitis and joint destruction in rheumatoid arthritis (RA) patients. However, the patterns of MRI-detected bone erosion, bone marrow edema (BME), synovitis, and tenosynovitis have received insufficient attention. Therefore, this study evaluated the patterns of bone erosion, BME, synovitis, and tenosynovitis, and calculated the RA-MRI score (RAMRIS) of patients with RA at the carpal and metacarpophalangeal (MCP) joints using MRI. Methods MRI datasets from 43 RA patients were analyzed. All patients had undergone MRI of one wrist. In addition, 36 patients had MCP joint images taken, and three had also received MRI of the contralateral wrist and MCP joints. The MR images were evaluated for bone erosion, BME, and synovitis in consensus by two blinded readers according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RAMRIS. The MRI-detected tenosynovitis was evaluated based on Haavardsholm’s tenosynovitis score. Results The capitate, lunate, triquetrum, and hamate bones were the most common sites of erosion and BME and showed the highest RAMRIS erosion and BME scores. Moreover, MRI-detected tenosynovitis was present in 78.3% of all patients with RA, and the extensor compartment 4 and flexor digitorum profundus and superficialis were frequently affected. Conclusions This study identified the distribution and prevalence of MRI-detected bone erosion, BME, synovitis, and tenosynovitis of the wrist and MCP joints in RA patients. The patterns of the MRI-detected abnormalities may help to select sites for the application of MRI protocols in clinical trials and practice.